Differential role of SLP-76 domains in T cell development and function

Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):884-9. doi: 10.1073/pnas.022619199. Epub 2002 Jan 15.

Abstract

The adapter SLP-76 is essential for thymocyte development. SLP-76(-/-) mice were reconstituted with SLP-76 deletion mutant transgenes to examine the role of SLP-76 domains in T cell development and function. The N-terminal domain deletion mutant completely failed to restore thymocyte development. Mice reconstituted with Gads-binding site and SH2 domain deletion mutants had decreased thymic cellularity, impaired transition from double to single positive thymocytes, and decreased numbers of mature T cells in the spleen. Calcium mobilization and extracellular signal-regulated protein kinase activation were decreased in the Gads-binding site mutant but almost normal in the SH2 domain mutant. T cells from both mutants failed to proliferate following T cell antigen receptor ligation. Nevertheless, both mutants mounted partial cutaneous hypersensitivity responses and normal T cell dependent IgG1 antibody responses. These results indicate differential roles for SLP-76 domains in T cell development, proliferation and effector functions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Binding Sites / genetics
  • Calcium / metabolism
  • Cell Differentiation
  • Cell Division
  • Isoenzymes / metabolism
  • Lectins, C-Type
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinases / metabolism
  • Mutation
  • Ovalbumin / immunology
  • Phospholipase C gamma
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / immunology*
  • Protein Structure, Tertiary
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Receptors, Interleukin-2 / metabolism
  • Sequence Deletion
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Type C Phospholipases / metabolism
  • src Homology Domains

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Isoenzymes
  • Lectins, C-Type
  • Phosphoproteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Interleukin-2
  • SLP-76 signal Transducing adaptor proteins
  • Ovalbumin
  • Mitogen-Activated Protein Kinases
  • Type C Phospholipases
  • Phospholipase C gamma
  • Calcium